Heart Rate Responses to Autonomic Challenges in Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) is accompanied by structural alterations and dysfunction in central autonomic regulatory regions, which may impair dynamic and static cardiovascular regulation, and contribute to other syndrome pathologies. Characterizing cardiovascular responses to autonomic challenges may provide insights into central nervous system impairments, including contributions by sex, since structural alterations are enhanced in OSA females over males. The objective was to assess heart rate responses in OSA versus healthy control subjects to autonomic challenges, and, separately, characterize female and male patterns. We studied 94 subjects, including 37 newly-diagnosed, untreated OSA patients (6 female, age mean±std: 52.1±8.1 years; 31 male aged 54.3±8.4 years), and 57 healthy control subjects (20 female, 50.5±8.1 years; 37 male, 45.6±9.2 years). We measured instantaneous heart rate with pulse oximetry during cold pressor, hand grip, and Valsalva maneuver challenges. All challenges elicited significant heart rate differences between OSA and control groups during and after challenges (repeated measures ANOVA, p<0.05). In post-hoc analyses, OSA females showed greater impairments than OSA males, which included: for cold pressor, lower initial increase (OSA vs. control: 9.5 vs. 7.3 bpm in females, 7.6 vs. 3.7 bpm in males), OSA delay to initial peak (2.5 s females/0.9 s males), slower mid-challenge rate-of-increase (OSA vs. control: −0.11 vs. 0.09 bpm/s in females, 0.03 vs. 0.06 bpm/s in males); for hand grip, lower initial peak (OSA vs. control: 2.6 vs. 4.6 bpm in females, 5.3 vs. 6.0 bpm in males); for Valsalva maneuver, lower Valsalva ratio (OSA vs. control: 1.14 vs. 1.30 in females, 1.29 vs. 1.34 in males), and OSA delay during phase II (0.68 s females/1.31 s males). Heart rate responses showed lower amplitude, delayed onset, and slower rate changes in OSA patients over healthy controls, and impairments may be more pronounced in females. The dysfunctions may reflect central injury in the syndrome, and suggest autonomic deficiencies that may contribute to further tissue and functional pathologies

Progressive gray matter changes in patients with congenital central hypoventilation syndrome

BACKGROUND: Congenital central hypoventilation syndrome (CCHS) patients show brain injury in areas that control chemosensory, autonomic, motor, cognitive, and emotion functions, which are deficient in the condition. Many of these abnormal characteristics are present from the neonatal period; however, it is unclear if tissue injury underlying the characteristics progressively worsens with time. We hypothesized that several brain areas in CCHS subjects would show increased gray matter volume loss over time. METHODS: We collected high-resolution T1-weighted images twice (four years apart) from 7 CCHS (age at first study, 16.1±2.7 years; 4 males) and 3 control subjects (15.9±2.1 years; 3 males) using a 3.0-Tesla MRI scanner, and evaluated regional gray matter volume changes with voxel-based-morphometry procedures. RESULTS: Multiple brain sites in CCHS, including frontal, prefrontal, insular and cingulate cortices, caudate nuclei and putamen, ventral temporal and parietal cortices, and cerebellar cortices showed significantly reduced gray matter volume over time. Only limited brain areas, including sensory, temporal, and medullary regions emerged with increased gray matter at the later age. CONCLUSIONS: CCHS patients show reduced gray matter volume with age progression in autonomic, respiratory, and cognitive regulatory areas, an outcome that may contribute to deterioration of functions found in the syndrome with increasing age